CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
免疫破坏是否驱动所有形式的骨髓衰竭？
英文原题：Does immune destruction drive all forms of bone marrow failure?
查看英文原题
Does immune destruction drive all forms of bone marrow failure?
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中文摘要
当前对骨髓衰竭（BMF）病理生理学的范式认为，免疫介导的造血干细胞和祖细胞（HSPC）破坏驱动了获得性再生障碍性贫血。相比之下，HSPC因衰老和/或凋亡而丢失导致遗传性BMF综合征中的BMF。在本期JCI中，Casado及其同事通过证明NK细胞依赖性、免疫介导的造血抑制和HSPC清除驱动范可尼贫血（FA）中的BMF，挑战了这种二分法概念。他们表明，基因毒性应激上调FA HSPC上的NK 细胞群2成员D配体（NKG2D-L），通过NKG2D受体激活导致NK细胞细胞毒性。抑制NKG2D-NKG2D-L相互作用增强了FA HSPC的克隆形成潜力，并改善了体内的血细胞减少。这些结果为开发免疫抑制疗法提供了替代靶点，以减少HSPC丢失并降低FA中血液系统恶性肿瘤的风险。
展开英文摘要原文
Current paradigms of bone marrow failure (BMF) pathophysiology suggest that immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs) drives acquired aplastic anemia. In contrast, loss of HSPCs due to senescence and/or apoptosis causes BMF in inherited BMF syndromes. In this issue of the JCI, Casado and colleagues challenge this dichotomous conception by demonstrating that NK cell-dependent, immune-mediated hematopoietic suppression and HSPC clearance drive BMF in Fanconi anemia (FA).
They show that genotoxic stress upregulates natural killer group 2 member D ligands (NKG2D-L) on FA HSPCs leading to NK cell cytotoxicity through NKG2D receptor activation. Inhibition of NKG2D-NKG2D-L interactions enhanced FA HSPC clonogenic potential and improved cytopenias in vivo. These results provide alternative targets for the development of immunosuppressive therapies to reduce HSPC loss and mitigate the risk of hematologic malignancies in FA.
论文信息
- 作者
- Dulmovits BM、Olson TS
- 单位
- Cell Therapy and Transplant Section, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.United States
- 文献类型
- 评论
- 期刊
- The Journal of clinical investigation2022 Aug 1
- 原文标识
- PubMed 35912855 · DOI 10.1172/JCI161288
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